Processes for the preparation of cyclic aldehydes

ABSTRACT

Processes for the preparation of cyclic aldehydes such as cedrenal which comprise treating the corresponding hydrocarbon to form a halo derivative of the hydrocarbon and oxidizing the halo derivative with an alkali-metal salt of 2-nitropropane to form the aldehyde.

United States Patent Wiegers et al.

[ Dec. 16, 1975 PROCESSES FOR THE PREPARATION OF CYCLIC ALDEHYDES Inventors: Wilhelmus J. Wiegers, Middletown;

John B. Hall, Rumson, both of NJ.

Assignee: International Flavors & Fragrances Inc., New York, NY.

Filed: Aug. 26, 1974 Appl. No.: 500,280

Related US. Application Data Division of Ser. No. 260,537, June 7, 1972, Pat. No. 3,869,5l6.

US. Cl. 260/598 Int. Cl. C07C 47/44 Field of Search 260/598, 648 R, 648 C References Cited OTHER PUBLICATIONS Semmler et 21]., Berichte der Deutches Chem. Ass., Vol. 45, (1912), 78679l. Hass et al., J.A.C.S., Vol 71, (1949), 1767-1769.

Primary ExaminerBernard l-lelfin Attorney, Agent,- or FirmBrooks Haidt Haffner & Delahunty [5 7] ABSTRACT 8 Claims, No Drawings 3 ,927 1 O9 l 2 where X is a halogen atom as herein described, in some PROCESSES FOR THE PREPARATION OF CYCLIC embodiments through an intermediate alpha-halo ALDEHYDES methylene derivative having the structure:

This is a division of US. Pat. application Ser. No. 5 X 260,537, filed June 7, 1972, now US. Pat. No. 3,869,516. 7

BACKGROUND OF THE INVENTION (In) The present invention provides processes for the 1 production of useful cyclic aldehydes, which processes are economical, straightforward, and based on the use of a minimum of reactants.

Cyclic aldehydeshave a variety of uses, and many such aldehydes are utilized as olfactory agents in perfume compositions and perfumed products and arti- The halo derivative is then oxidized to provide cedrenal having the structure:

cles. An instance of such use is the material called v o cedrenal. This compound has desirable woody notes E and can comprise various perfume compositions.

In the past it has been customary to prepare cedrenal by a series of reactions carried out on a suitable starting material. One such preparation is shown in Swiss Pat. No. 485,629. This prior art process is shown to start with alpha-cedrene which is converted to epoxycedrene y treatment with Peracetic acid in a reaction The alpha-cedrene utilized in carrying out the presmedium- The epoxycedrene is treated with lithium ent invention is commercially available and can be an e iam to p o eedrenol and the eedrenel is obtained from a natural source or by the dehydration of subsequently halogenated with phosphorus tribromide cedrol. Cedrol can be obtained from the oil of cedar and then oxidized with 2-nitropropane to provide and other trees. It is preferred that the alpha-cedrene cedrenal. used as a raw material be substantially pure, although Halogenation of alpha-pinene with chlorine to prolower purity materials can be used to carry out the vide a chloro isomer of the pinene is shown by Tishreaction described herein with lower yields.

chenko and Matveyev, Zh. Obshch. Khim. 20, 1950, The initial step of the process is direct halogenation Oxidation reactions with nitropropane ar shown i of alpha-cedrene to provide either the halo derivative J.A.C.S. 81,4223 and British Pat. No. 803,765. Various directly o e to pro ide the alpha-halo methylene hal ati r ti ar l shown b K k derivative which is then rearranged to provide the halo Org Khim 6(7), 133 and Lauchenuelet a1 derivative. In the preferred embodiment of the inven- Helvetica chimica Ada 34(5), 5 4 tion,the halo derivative is provided directly. The halogens contemplated for use herein are chlorine, bro- THE INVENTION mine, and iodine, with chlorine being the preferred halogen. The halogen is introduced directly into the alpha-cedrene, and in the case of chlorine, the halogen is bubbled into the cedrene. It is possible to utilize a reaction vehicle during this halogenation step but in certain embodiments of the invention it is preferred that no vehicle be used.

The direct halogenation in the absence of a basic material is carried out at temperatures from about 75 to about 175C, with the preferred temperature range for chlorination being from about 125l35C, so as to provide a relatively rapid reaction rate with good conm trol of the reaction. At these temperatures the time of halogen addition can very from about one to about 25 hours, with periods from four to about eight hours being preferred utilizing chlorine at a temperature of l25l35C. Those skilled in the art will appreciate from the present disclosure that the foregoing ranges m 15 Peacted to Provide"a h derivative havmg the given for batch preparation can be suitably modified Structure; 4 for a continuous production procedure, depending upon the particular halogen and reaction apparatus utilized. I

The molar ratio of halogen to cedrene is desirably (In from about 0.5 to about 1.5 moles of halogen per mole of cedrene. It is generally preferred to use amounts of halogen close to the stoichiometric, and ratios of about 0.8 to about 1.1 moles of halogen per mole of cedrene are preferred. The halogenation can be carried out Briefly, the present invention provides a method for simply and conveniently preparing cedrenal in good yields. The process comprises reacting alpha-cedrene 5 with a halogen to obtain a halo derivative thereof and then oxidizing the halo derivative with 2-nitropropane to obtain cedrenal.

As used herein, alpha-cedrene is a compound having the structure: a 5o over a range of pressure, with atmospheric or slightly subatmospheric pressure being. desirable. Subatmospheric pressures can give good results in certain embodiments of the invention, since hydrogen halide is removed from the reaction mass. This halogenation method provides the halo-cedrene derivative which can be directly oxidized to the aldehyde as more fully described herreinafter.

The halogenation can also be carried out to provide the alpha-chloro methylene derivative by reacting the halogen with cedrene in the presence of a basic material such as an alkai metal carbonate or bicarbonate or an alkaline earth metal carbonate or bicarbonate. A preferred basic material in certain embodiments hereof is sodium carbonate.

The molar ratio of basic material to halogen is desirably from about 0.4 to about one mole of alkaline material to one mole of halogen, with ratios of from 0.6:] to 08:1 being preferred. The molar ratio of halogen to alpha-cedrene and the halogens utilized are the same as those set forth above in connection with the direct halogenation. It is desirable in this embodiment of the method that a vehicle be utilized, and water is a preferred vehicle. Other vehicles such as lower alkyl ethers like diethyl ether, hydrocarbons like hexane, and haloge'nated solvents such as carbon tetrachloride can also be present. This reaction is desirably carried out at temperatures from about to about 75C, with preferred embodiments of the invention utilizing temperatures of l030C. At these temperatures, reaction times of from about one to about 25 hours are used with the reaction preferably being carried out in from four to eight hours.

The pressure utilized can be somewhat subatmospheric or superatmospheric, but atmospheric pressures are preferred .for yield and convenience of operation-This procedure provides the alpha-halo methylene derivative; v

The halo methylene can, if desired, be separated from the reaction mixture and purified by conventional means. It is however desirable in certain'aspects of this invention that the halo methylene derivative-be isomerized directly to provide the halo derivative. The isomerization is preferably carried out by heating, desirably at temperatures from about 75 to about 175C, with the preferred temperature being l25l35C.

The time required for good yields in the isomerization varies inversely with the temperatures utilized. Generally, it is desirable to conduct the isomerization during a time of from about one to about 25 hours. When the isomerization is conducted at the preferred temperatures of l25-l 35C, substantial completion is usually obtained'from three to six hours.

The reaction can be carried out at subatmospheric or superatmospheric pressure, but it is generally preferred to use atmospheric pressure in certain embodiments hereof. If desired, the isomerization can be a catalytic one carried out with suitable metal salts. Isomerization can be carried out on a continuous basis as can the halogenation to provide the halo-methylene derivative.

It will accordingly be seen from the present disclosure that the halogenation of the cedrene is desirably carried out in the temperature range of 0 to .175C. While the halogenation in the presence of a basic material requires an extra step to isomerize the alpha-halo methylene derivative to the halo derivative, this reaction can be carried out at ordinary room temperatures. Hence, it can be advantageous in some embodiments to 4 utilize the lower temperature route, despite the extra step involved.

After preparation of the halo derivative, it is directly oxidized to cedrenal with an alkali-metal salt of 2-nitropropane, such as the potassium salt of 2-nitropropane. The nitropropane oxidation is carried out by treating the halo derivative at temperatures of from about to about C with the alkali-metal salt of 2-nitropropane. The preferred temperature of this step of the process is 8595C. Reaction times of from about two to about ten hours are used, with times of from five to seven hours being preferred.

The oxidation is preferably carried out in the presence of an inert vehicle, desirably a lower alcohol having from one to four carbon atoms. A preferred vehicle is isopropyl alcohol.

A substantially stoichiometric amount of alkali metal hydroxide in relation to the'2-nitropropane is desirably used to form the alkali metal salt in situ. It is preferred to utilize the 2-nitropropane in slight excess of the alkali metal hydroxide.

During the oxidation reaction, it is desirable to have a small quantity of alkali metal iodide, such as potassium iodide, present in the vehicle. Amounts of iodide on the order of 0.5 to 1% of the quantity of halo derivative are utilized. All parts, proportions, percentages, and ratios herein are by weight unless otherwise indicated.

It is preferred to carry out the oxidation by feeding the halo derivative to a mixture of vehicle which is in admixture with the nitropropane salt.

After the oxidation reaction has been completed, the cedrenal so obtained is then washed, dried, and freed of vehicle and other ingredients of the reaction mixture by conventional methods. The cedrenal can be purifiedor isolated by conventional techniques such as distillation, extraction; preparative chromatographic techniques and the like. A preferred procedure is vacuum distillation.

The following Examples are given to illustrate embodiments of the invention as it is now preferred to practice it. It will be understood that these examples are illustrative, and the invention is not to be considered as restricted thereto except as indicated in the appended claims. I

EXAMPLE 1 Preparation of Chloro Derivative A 250 ml reaction flask equipped with stirrer, thermometer, reflux condenser, chlorine inlet tube, gas bubbler outlet, heating mantle, and temperature controller is charged with 102 g of alpha-cedrene, and the contents are heated to C. This temperature is maintained during a 3% hour time during which 37 g of chlorine is sparged into the reaction mass.

The reaction mass is maintained at a temperature of 130C for an additional hour. Infrared (IR) spectrometric analysis shows that the product is the chloro cedrene derivative, [1 on Page 3.

EXAMPLE II Oxidation of Chloro Derivative A 12-liter reaction flask equipped with stirrer, thermometer, reflux condenser, 2-liter dropping funnel with nitrogen line, and heating mantle is charged with 1230 g of isopropyl alcohol, 537 g of potassium hydroxide flakes, and 7.5 g of potassium iodide. The reaction mass is heated to reflux, 804 g of 2-nitropropane is placed in the dropping funnel, and the nitropropane is added to the flask contents during minutes while the temperature is maintained in the range of 8995C and 6 mately 90 mm Hg vacuum, held for 5 hours at 150C to isomerize it to the chloro derivative (compound ll on Page 3) in a yield of 1049 g of crude compound ll.

This derivative is oxidized to produce cedrenal as the flask contents are stirred. The potassium salt of 5 d ribed herein.

Z-nitropropane is thus formed.

The reaction mass is refluxed for 15 minutes after addition of the nitropropane is complete, while 2200 g of the chloro derivative prepared according to the procedure illustrated in Example I is placed in the dropping funnel. The temperature of the mass is maintained at 8693C while the chloro derivative is added over a period of 30 minutes with stirring. The reaction mass is then refluxed for an additional five hours with stirring.

After addition of the chloro derivative is complete, 779 g of isopropyl alcohol is removed from the mass by distillation. Four liters of water is then added, and the reaction mass is stirred for 15 minutes, whereupon an aqueous phase and an organic phase form. The aqueous phase is removed from the organic phase and is extracted with toluene, the toluene extract being combined with the organic phase. The organic phase is then washed thrice with 750 ml portions of 5% aqueous sodium chloride. The toluene is stripped off and the material is rushed over using a three-inch packed column. The distillate is redistilled using a three-foot packed column at a vapor temperature of l29-l30C under 2.5-3.0 mm Hg.

IR, nuclear magnetic resonance (NMR) and mass spectral analyses confirm that the 690 g of product is cedrenal.

EXAMPLE [I] A three-liter reaction flask equipped with a stirrer, reflux condenser, dropping funnel, chlorine inlet, two gas bubblers, and cooling bath is charged with 600 g of water and 297 g of sodium carbonate. The flask contents are stirred for 30 minutes and then 1020 g of alpha-cedrene are added. While the temperature of the flask contents is maintained at l5-20C, chlorine gas is bubbled through the mixture for five hours at the rate of 68 g an hour. Approximately halfway through the addition of chlorine, 300 g of water is added to improve the ease of mixing.

After chlorine addition is complete 700 g of water is added and the flask contents are stirred for 30 minutes. The stirring is discontinued, the flask contents separate into an aqueous and an organic phase, and the aqueous phase is extracted with 250 g of toluene. The toluene extract is combined with the organic layer and washed twice with 250 g of 5% aqueous sodium chloride solution.

The washed material is the alpha-chloro methylene derivative (Formula III on Page 3). The toluene is stripped off and the material is placed under approxi- What is claimed is:

l. A process for the production of cyclic carbonyl compounds which comprises reacting alpha-cedrene with a halogen at temperatures of 0 to C in the presence of a basic material to provide an alpha-halo methylene derivative having the structure isomerizing the alpha-halo methylene derivative by heating to a temperature of from 75 to 175C to form a halo derivative having the structure and oxidizing the halo derivative with an alkali metal salt of 2-nitropropane to obtain cedrenal, wherein X is chloro, bromo, or iodo.

2. A process according to claim 1 wherein X is chloro.

3. A process according to claim 1 wherein the reaction is carried out in the presence of an alkali metal carbonate or bicarbonate or an alkaline earth carbonate or bicarbonate.

4. A process according to claim 3 wherein the basic material is sodium carbonate.

5. A process according to claim 1 wherein the heating is carried out for from 1 to 25 hours.

6. A process according to claim 1 wherein the oxidation is carried out at 70 to C.

7. A process according to claim 6 wherein the oxidation is carried out in the presence of an inert vehicle, and an alkali metal iodide.

8. A process according to claim 1 wherein the alkali metal is potassium. 

1. A PROCESS FOR THE PRODUCTION OF CYCLIC CARBONYL COMPOUNDS WHICH COMPRISES REACTING ALPHA-CEDRENE WITH A HALOGEN AT TEMPERATURES OF 0* TO 75*C IN THE PRESENCE OF A BASIC MATERIAL TO PROVIDE AN ALPHA-HALO METHYLENE DERIVATIVE HAVING THE STRUCTURE
 2. A process according to claim 1 wherein X is chloro.
 3. A process according to claim 1 wherein the reaction is carried out in the presence of an alkali metal carbonate or bicarbonate or an alkaline earth carbonate or bicarbonate.
 4. A process according to claim 3 wherein the basic material is sodium carbonate.
 5. A process according to claim 1 wherein the heating is carried out for from 1 to 25 hours.
 6. A process according to claim 1 wherein the oxidation is carried out at 70* to 100*C.
 7. A process according to claim 6 wherein the oxidation is carried out in the presence of an inert vehicle, and an alkali metal iodide.
 8. A process according to claim 1 wherein the alkali metal is potassium. 